Pathologies liées aux déficits du cycle de Krebs

Published on Apr 1, 2018in Revue Francophone Des Laboratoires
· DOI :10.1016/s1773-035x(18)30120-5
Paule Bénit34
Estimated H-index: 34
(French Institute of Health and Medical Research),
Sylvie Bortoli6
Estimated H-index: 6
(Paris Descartes University)
+ 2 AuthorsPierre Rustin79
Estimated H-index: 79
(French Institute of Health and Medical Research)
Resume Chez l'homme, les dysfonctions des enzymes du cycle de Krebs liees a des mutations causent des encephalopathies severes du jeune enfant, ou differents types de tumeurs et de cancers touchant differents organes. Ainsi des mutations des genes de la succinate-deshydrogenase ont ete identifiees dans des formes familiales de pheochromocytomes et paragangliomes. Les mutations du gene de la fumarase s'observent dans des leiomyomes uterins en association avec des cancers renaux, mais des cas d'encephalopathies de l'enfant ont aussi ete observes. Les mutations des genes de l'isocitrate-deshydrogenase peuvent representer jusqu'a 20% des leucemies myeloides aigues et jusqu'a 80% dans certains gliomes. On ne sait actuellement expliciter la diversite des consequences possibles de ces mutations : encephalopathies versus cancers, nature des tissus affectes, cinetique variable d'apparition des symptomes. Il semble en revanche etabli que les anomalies dans les equilibres metaboliques qui resultent de ces mutations soient a la base des processus tumoraux en modulant l'activite d'hydroxylases susceptibles d'affecter certains facteurs de transcriptions, mais aussi la methylation de l'ADN et les histones. Dans ce contexte, il semble etonnant que soient largement utilises certains fongicides dont l'effet est de bloquer une etape centrale du cycle de Krebs, la succinate-deshydrogenase. Le principe de precaution voudrait sans aucun doute de reevaluer urgemment la necessite de l'usage de telles substances pour l'homme et l'environnement.
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Published on Jan 1, 1938in Biochemical Journal 3.86
H. A. Krebs40
Estimated H-index: 40
(University of Sheffield),
Ernest Salvin1
Estimated H-index: 1
(University of Sheffield),
William Arthur Johnson3
Estimated H-index: 3
(University of Sheffield)
47 Citations Source Cite
Published on Nov 4, 1994in Journal of Biological Chemistry 4.01
Marc Yudkoff46
Estimated H-index: 46
David Nelson29
Estimated H-index: 29
+ 1 AuthorsMaria Erecińska56
Estimated H-index: 56
Abstract The flux through different segments of the tricarboxylic acid cycle was measured in rat brain synaptosomes with gas chromatography-mass spectrometry using either deuterated glutamine or [13C]aspartate. The flux between 2-oxoglutarate and oxaloacetate was estimated to be 3.14 and 4.97 nmol/min/mg protein with and without glucose, respectively. These values were 3-5-fold faster than the flux between oxaloacetate and 2-oxoglutarate (0.92 nmol/min per mg protein) measured in the presence of...
105 Citations
Published on Nov 15, 2014in International Journal of Cancer 7.36
Aurélie Morin9
Estimated H-index: 9
(Paris Descartes University),
Eric Letouzé21
Estimated H-index: 21
+ 1 AuthorsJudith Favier33
Estimated H-index: 33
(Paris Descartes University)
Although the alteration of cellular metabolism in cancer was reported by Warburg in the early 1930s, a regain of interest in cancer metabolism has more recently followed the discovery of germline or somatic mutations in genes coding for metabolic enzymes (succinate dehydrogenase, fumarate hydratase and isocitrate dehydrogenase) that are associated with tumor susceptibility. Mutations in these genes are found in numerous tumor types including paragangliomas, kidney cancers, leiomyomas, glioblasto...
58 Citations Source Cite
Published on Aug 1, 2016in Neurobiology of Disease 5.23
Douglass M. Turnbull94
Estimated H-index: 94
(Newcastle University),
Pierre Rustin79
Estimated H-index: 79
(French Institute of Health and Medical Research)
Abstract The major progress made in the identification of the molecular bases of mitochondrial disease has revealed the huge diversity of their origin. Today up to 300 mutations were identified in the mitochondrial genome and about 200 nuclear genes are possibly mutated. In this review, we highlight a number of features specific to mitochondria which possibly participate in the complexity of these diseases. These features include both the complexity of mitochondrial genetics and the multiplicity...
16 Citations Source Cite
Published on Jan 1, 2002in Nature Genetics 27.13
Ian Tomlinson98
Estimated H-index: 98
(Cancer Research UK),
N. Afrina Alam5
Estimated H-index: 5
(Cancer Research UK)
+ 28 AuthorsShamima Rahman1
Estimated H-index: 1
(University College London)
Uterine leiomyomata (fibroids) are common and clinically important tumors, but little is known about their etiology and pathogenesis. We previously mapped a gene that predisposes to multiple fibroids, cutaneous leiomyomata and renal cell carcinoma to chromosome 1q42.3-q43 (refs 4-6). Here we show, through a combination of mapping critical recombinants, identifying individuals with germline mutations and screening known and predicted transcripts, that this gene encodes fumarate hydratase, an enzy...
994 Citations Source Cite
Published on Oct 1, 1995in Nature Genetics 27.13
Thomas Bourgeron52
Estimated H-index: 52
(French Institute of Health and Medical Research),
Pierre Rustin79
Estimated H-index: 79
(French Institute of Health and Medical Research)
+ 5 AuthorsAgnès Rötig65
Estimated H-index: 65
(French Institute of Health and Medical Research)
We now report a mutation in the nuclear–encoded flavoprotein (Fp) subunit gene of the succinate dehydrogenase (SDH) in two siblings with complex II deficiency presenting as Leigh syndrome. Both patients were homozygous for an Arg554Trp substitution in the Fp subunit. Their parents (first cousins) were heterozygous for the mutation that occurred in a conserved domain of the protein and was absent from 120 controls. The deleterious effect of the Arg to Trp substitution on the catalytic activity of...
535 Citations Source Cite
Published on Jun 1, 1994in Journal of Clinical Investigation 13.25
T Bourgeron1
Estimated H-index: 1
Dominique Chretien45
Estimated H-index: 45
+ 7 AuthorsPierre Rustin79
Estimated H-index: 79
Abstract We report an inborn error of the tricarboxylic acid cycle, fumarase deficiency, in two siblings born to first cousin parents. They presented with progressive encephalopathy, dystonia, leucopenia, and neutropenia. Elevation of lactate in the cerebrospinal fluid and high fumarate excretion in the urine led us to investigate the activities of the respiratory chain and of the Krebs cycle, and to finally identify fumarase deficiency in these two children. The deficiency was profound and pres...
116 Citations Source Cite
Published on Dec 1, 2001in American Journal of Human Genetics 8.86
Anne-Paule Gimenez-Roqueplo53
Estimated H-index: 53
Judith Favier33
Estimated H-index: 33
(Collège de France)
+ 5 AuthorsXavier Jeunemaitre63
Estimated H-index: 63
(Collège de France)
Hereditary paragangliomas are usually benign tumors of the autonomic nervous system that are composed of cells derived from the primitive neural crest. Even though three genes (SDHD, SDHC, and SDHB), which encode three protein subunits of cytochrome b of complex II in the mitochondrial respiratory chain, have been identified, the molecular mechanisms leading to tumorigenesis are unknown. We studied a family in which the father and his eldest son had bilateral neck paragangliomas, whereas the sec...
295 Citations Source Cite
Published on May 1, 2015in Analytical and Bioanalytical Chemistry 3.31
Antonio Abad Fuentes16
Estimated H-index: 16
(Spanish National Research Council),
Eric Ceballos-Alcantarilla2
Estimated H-index: 2
(University of Valencia)
+ 3 AuthorsFrancesc A. Esteve Turrillas18
Estimated H-index: 18
(Spanish National Research Council)
In recent years, a second generation of succinate-dehydrogenase-inhibitor (SDHI) fungicides has been introduced into the market for effective treatment of fruit and vegetable crops, with fluxapyroxad, boscalid, fluopyram, penflufen, bixafen, penthiopyrad, and isopyrazam being some of the members of this new class of agrochemical. We herein report the development of an analytical procedure for the determination of residues of these SDHI fungicides in food samples, based on a modification of the Q...
19 Citations Source Cite
Published on Jun 1, 2013in Current Opinion in Plant Biology 7.35
Shaobai Huang23
Estimated H-index: 23
(University of Western Australia),
A. Harvey Millar74
Estimated H-index: 74
(University of Western Australia)
Succinate dehydrogenase (SDH) oxidises succinate to fumarate as a component of the tricarboxylic acid cycle and ubiquinone to ubiquinol in the mitochondrial electron transport chain. Studies of SDH mutants have revealed far-reaching effects of altering succinate oxidation in plant cells. The plant SDH complex composition, structure and assembly are all beginning to be understood but the implications of the divergence across eukaryotes is still unclear. We propose an integration of the reported p...
42 Citations Source Cite
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